1. Field of the Invention
The present invention relates to a new method of diagnosing malignant hyperthermia (MH) using a few milliliters of blood.
2. Background Art
MH is a serious complication of anesthesia with a high risk of death. The symptom (muscle rigidity and/or fever) is manifested when a genetically MH-susceptible individual receives general anesthesia or succinylcholine (a commonly used muscle relaxant) in the operating room. Currently, the only reliable method of screening this disorder is to surgically remove a piece of muscle from the suspect, and perform an elaborate laboratory test to investigate the effect of halothane (sometimes in conjunction with succinylcholine or caffeine) on the contractility of excised muscle fibers. This is such a stressful test for the suspect that many of possible patients (family members and blood-related relatives of a MH patient) do not want to take the test.
MH is observed in both human and pig. Isolating sarcoplasmic reticulum from skeletal muscle of genetically MH-susceptible pigs, the inventor pioneered to find functional structural abnormalities in the membranes of the sarcoplasmic reticulum.
(i) Functional: The sarcoplasmic reticulum of susceptible pigs is abnormally permeable to calcium, and halothane greatly enhances the calcium release from the sacroplasmic reticulum.
(ii) Structural: Halothane greatly fluidizes the membrane structure of the sarcoplasma reticulum. (See Ohnishi et al, FEBS LETTERS, Vol. 161, No. 1, September, 1983, pages 103-107; Ohnishi et al, Archiv. Biophys. Biochem., Vol. 247, No. 2, June, 1986, pages 294-301; and Ohnishi, Biochim. Biophys. Acta, Vol. 897, No. 2, February, 1987, pages 261-268.)
Using blood drawn from both MH-positive pigs and MH-positive patients, the inventor found that membranes of red blood cells have structural abnormality similar to that found in the sarcoplasmic reticulum. This is the basis that both sarcoplasmic reticulum and red blood cells may be regulated by the same gene, and that this genetic defect of skeletal muscle could be diagnosed by using red blood cells.